Target intelligence / Profile preview

Solute carrier family 22 member 12 (URAT1) (URAT1)

Target
URAT1
Molecular classification
Transporter [2, 3], Solute carrier family 22 [6, 16], Organic anion transporter (OAT) [2, 9]
01

Overview

Human URAT1, encoded by the SLC22A12 gene, is a key renal transporter located on the apical membrane of proximal tubular epithelial cells [2, 6]. It functions as an electroneutral organic anion exchanger, primarily responsible for the reabsorption of filtered urate from the tubular lumen back into the blood in exchange for intracellular anions like lactate or nicotinate [1, 14]. This process is critical for maintaining systemic uric acid homeostasis, as approximately 90% of filtered urate is reabsorbed via this pathway [10, 11]. Dysregulation of URAT1, such as overactivity or high expression, is a major contributor to hyperuricemia and the subsequent development of gout [2, 16]. Conversely, loss-of-function mutations in the SLC22A12 gene lead to renal hypouricemia type 1, a condition characterized by low serum urate levels and a risk of exercise-induced acute kidney injury and nephrolithiasis [3, 13]. URAT1 is the primary therapeutic target for uricosuric drugs, including lesinurad, benzbromarone, and probenecid, which lower serum uric acid by inhibiting its reabsorption [10, 12]. These drugs effectively manage gout but require monitoring for potential renal safety concerns, such as kidney stone formation or acute renal failure, due to the increased concentration of uric acid in the urine [15].

Other names
SLC22A12RSTOAT4LUrate anion exchanger 1Urate:anion antiporter SLC22A12Renal-specific transporterOrganic anion transporter 4-like protein
02

Mechanism of action

Inhibition of urate reabsorption in the renal proximal tubule [2, 10, 11]

03

Biological functions

Urate transport [1, 7]Renal reabsorption of urate [2, 11]Electroneutral anion exchange [1, 14]Maintenance of blood uric acid homeostasis [2, 16]
04

Disease associations

Gout [2, 10]Hyperuricemia [6, 17]Renal hypouricemia type 1 [3, 13]Nephrolithiasis (kidney stones) [3, 15]Hypertension [2, 16]
05

Safety considerations

Nephrolithiasis (urolithiasis) [3, 15]Acute kidney injury (AKI) [13, 15]Hepatotoxicity (e.g., with benzbromarone) [10]Drug-drug interactions [2, 9]
06

Interacting drugs

Lesinurad [2, 10]

7 more in the full profile.

07

Biomarkers

Serum uric acid (sUA) level [2, 17]Fractional excretion of uric acid (FEUA) [14]Urinary uric acid excretion [15]

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